Effects of prostaglandin E 2, indomethacin and adenosine deaminase on basal and insulin-stimulated glucose metabolism in human adipocytes

Abstract

The effects of prostaglandin E 2 were studied on glucose metabolism (3- O-methylglucose transport, CO 2 production and lipogenesis) in human adipocytes. Initially, the effects of endogenously produced adenosine and prostaglandins were indirectly demonstrated by using adenosine deaminase and indomethacin in the incubations. From these studies it was found that adenosine deaminase (5 μg/ml) had a pronounced effect on adipocyte glucose metabolism in vitro. In the basal (nonhormonal-stimulated) state, glucose transport, CO 2 production and lipogenesis were inhibited by about 30% ( P<0.05). Furthermore, adenosine deaminase significantly inhibited the isoproterenol- and insulin-stimulated CO 2 production and lipogenesis ( P<0.01). Indomethacin (50 μM) had a consistently inhibitory effect on the insulin-stimulated CO 2 production ( P<0.05), whereas indomethacin had no significant effects on basal or isoproterenol-stimulated glucose metabolism. In contrast to the relatively minor effect of endogenous prostaglandins, the addition of exogenous prostaglandin E 2 significantly stimulated the glucose transport, glucose oxidation and lipogenesis in human adipocytes, especially in the presence of adenosine deaminase. Half-maximal stimulation was obtained at prostaglandin E 2 concentrations of 2.2, 0.8 and 0.8 nM, respectively. The effect of prostaglandin E 2 was specific, since the structurally related prostaglandin, prostaglandin F 2α, had practically no effect on glucose metabolism. The maximal effect of prostaglandin E 2 (1 μM) on glucose metabolism was 30–35% of the maximal insulin (1 nM) effect. When insulin and prostaglandin E 2 were added together, the effect of prostaglandin E 2 on glucose metabolism was additive at all insulin concentrations tested.